• ALANKAR SHRIVASTAVA Department of Pharmaceutical Quality Assurance, KIET School of Pharmacy, Ghaziabad-Meerut Road (NH-58) Muradnagar-201206, District Ghaziabad.






The diseases involve heart and blood vessels are classified under cardiovascular diseases. Hypertension (HTN) is a disorder of the CV system characterized by elevated arterial blood pressure. Pulsatile drug delivery systems are on highlight today. This is due to their distinct advantage of releasing drug as the circadian rhythm of the disease. The beta-blockers are first-line therapy for the HTN. Hence, researches related to such modified formulations of these drugs are of need to increase the patient compliance and convenience. This review describes the various such systems published in literature. This also includes a brief description about circadian rhythm and beta-blockers. The researchers involved in the development of modified release formulations are the main target audience for this review.


Download data is not yet available.

Author Biography

ALANKAR SHRIVASTAVA, Department of Pharmaceutical Quality Assurance, KIET School of Pharmacy, Ghaziabad-Meerut Road (NH-58) Muradnagar-201206, District Ghaziabad.

Associate Professor,

Department of Quality Assurance


Coons JC, Empey P. Drug Metabolism in Cardiovascular Disease. Drug Metabolism in Diseases. Philadelphia, PA: Elsevier Inc.; 2017. p. 139.

Taylor DA, Abdel-Rahman AA. Novel strategies and targets for the management of hypertension. Adv Pharmacol 2009;57:291-345.

Huan Y, Townsend RR. Evaluation and Management of Hypertension. St. Louis, MO: Elsevier; 2014. p. 590-600.

Yagil C, Yagil Y. The genomics of hypertension. In: Ginsburg G, Willard H, editors. Essentials of Genomic and Personalized Medicine. New York: Elsevier Inc.; 2010. p. 259.

Scriabine A. Hypertension. In: Comprehensive Medicinal Chemistry II. Vol. 6. Oxford, UK: Elsevier Ltd.; 2007. p. 705.

Bunag R. Essential Hypertension. xPharm: The Comprehensive Pharmacology Reference. Amsterdam: Elsevier Inc.; 2007. p. 1-6.

Bagga A, Jain R, Vijayakumar M, Kanitkar M, Ali U. Evaluation and management of hypertension. Indian Pediatr 2007;44:103-21.

Messerli FH, Williams B, Ritz E. Essential hypertension. Lancet 2007;370:591-603.

Skene DJ, Arendt J. Human circadian rhythms: Physiological and therapeutic relevance of light and melatonin. Ann Clin Biochem 2006;43:344-53.

Czeisler CA, Gooley JJ. Sleep and circadian rhythms in humans. Cold Spring Harb Symp Quant Biol 2007;72:579-97.

Wirz-Justice A. How to measure circadian rhythms in humans. Medicographia 2007;29:84-90.

Ko CH, Takahashi JS. Molecular components of the mammalian circadian clock. Hum Mol Genet 2006;15 Spec No 2:R271-7.

Vitaterna MH, Takahashi JS, Turek FW. Overview of Circadian Rhythms. Available from: https://www.pubs.niaaa.nih.gov/publications/arh25-2/85-93.htm.

Hastings M, O’Neill JS, Maywood ES. Circadian clocks: Regulators of endocrine and metabolic rhythms. J Endocrinol 2007;195:187-98.

Johnston JD, Ordovás JM, Scheer FA, Turek FW. Circadian rhythms, metabolism, and chrononutrition in rodents and humans. Adv Nutr 2016;7:399-406.

Reutrakul S, Knutson KL. Consequences of circadian disruption on cardiometabolic health. Sleep Med Clin 2015;10:455-68.

Unger T, Paulis L, Sica DA. Therapeutic perspectives in hypertension: Novel means for renin–angiotensin–aldosterone system modulation and emerging device-based approaches. Eur Heart J 2014;32:2739-47.

Gheorghiade M, Eichhorn EJ. Practical aspects of using beta-adrenergic blockade in systolic heart failure. Am J Med 2001;110 Suppl 7A:68S-73.

Tobe SW. Adrenergic receptor blockers in hypertension. Can J Cardiol 2014;30:S1-2.

McHugh J, Pokhrel P, Barber K, Liu G. Beta-blockers in the management of cardiovascular diseases. Osteopath Fam Physician 2010;2:131-8.

Cullington D, Yassin A, Cleland J. Beta-blockers in the treatment of cardiovascular disease. Prescriber 2008;19:31-9.

Eldrup-Jorgensen J. Measuring quality and the story of beta blockers. J Vasc Surg 2011;53:845-55.

Vardanyan R, Hruby V. Antihypertensive drugs. In: Synthesis of Best-Seller Drugs. Amsterdam, Netherlands: Elsevier; 2016. p 331-2.

Charoenthai N, Wickramanayaka A, Sungthongjeen S, Puttipipatkhachorn S. Use of cassava starch nanocrystals to make a robust rupturable pulsatile release pellet. Drug Deliv Sci Technol 2018;47:283-90.

Davoodi P, Lee LY, Xu Q, Sunil V, Sun Y, Soh S, et al. Drug delivery systems for programmed and on-demand release. Adv Drug Deliv Rev 2018;132:104-38.

Bauskar MD, Nandedkar SY, Wagh RD. Formulation design and optimization of pulsatile release tablet of doxofylline with swelling and erodiable layers for treatment of nocturnal asthma. Int J Pharm Pharm Sci 2011;3 Suppl 5:218-23.

Domala R, Eedara BB, Dhurke RK. Development of pulsatile drug delivery system using novel solubilizers for antihypertensive drug. Int J Pharm Pharm Sci 2014;6:659-64.

Jain D, Raturi R, Jain V, Bansal P, Singh R. Recent technologies in pulsatile drug delivery systems. Biomatter 2011;1:57-65.

Hardison S, Wan W, Dodson KM. The use of propranolol in the treatment of subglottic hemangiomas: A literature review and meta-analysis. Int J Pediatr Otorhinolaryngol 2016;90:175-80.

Bylund DB, Gruetter CA. Propranolol. In: Enna SJ, Bylund DB, editor. xPharm: The Comprehensive Pharmacology Reference. Boston, MA: Elsevier Inc.; 2007.

Lin-Wen L, Sheng-Feng H, Hong-Liang L, Hsiu OH, Ming-Thau S. Development of timely controlled-release systems for chronotherapy of propranolol with minimization of the pH Effect in the simulated gastrointestinal medium. J Food Drug Anal 2013;21:115-25.

Newton AM, Kaur B, Indana VL, Rajesh KS. Chronotherapeutic drug delivery of pectin Vs. Guar gum, xanthan gum controlled release colon targeted directly compressed propranolol HCl matrix tablets. SAJ Pharm Pharmacol 2014;1:201.

Gruetter CA. Metoprolol. In: Enna SJ, Bylund DB, editors. xPharm: The Comprehensive Pharmacology Reference. Boston: Elsevier; 2007. p. 1-7.

Borgaonkar PA, Bushetti SS, Najmuddin M. Formulation and evaluation of pulsatile drug delivery system of metoprolol tartarate using core in cup tablet. Am J Med Med Sci 2012;2:114-22.

Pavani D, Krishna EH, Ramesh S. Development and evaluation of metoprolol tartrate chronotherapeutic drug delivery system. J Innov Pharm Biol Sci 2015;2:53-63.

Vonica-Gligor AL, Tomuţă I, Leucuţa SE. Piecewise function parameters as responses of the design of experiment in the development of a pulsatile release chronopharmaceutical system. Acta Pharm 2016;66:173-89.

Emami J, Kazemali MR. Design and in vitro evaluation of a novel controlled onset extended-release delivery system of metoprolol tartrate. Res Pharm Sci 2016;11:81-92.

Salunkhe AK, Dias RJ, Mali KK, Mahajan NS, Ghorpade VS. Formulation and evaluation of floating pulsatile drug delivery system of metoprolol tartrate. Pharm Lett 2011;3:147-60.

Kumar KS, Kotaiah MR, Rao MP. Formulation and evaluation of pulsatile drug delivery system of metoprolol tartrate. Int J Pharm Res Biosci 2013;2:246-57.

Agrawal SS, Dadarwal SC, Madan S. Formulation and in vitro characterization of chronopharmaceutical drug delivery system of metoprolol tartrate using hydroxypropyl cellulose. J Chronother Drug Deliv 2011;2:95-101.

Taranalli SS, Dandagi PM, Mastiholimath VS. Development of hollow/porous floating beads of metoprolol for pulsatile drug delivery. Eur J Drug Metab Pharmacokinet 2015;40:225-33.

Mishra A, Imam SS, Aqila M, Ahad A, Uzzafar A, Sultana Y, et al. Carvedilol nano lipid carrier: formulation, characterization and in-vivo evaluation. Drug Deliv 2016;23:1486-94.

Zhu LL, Zhou Q, Yan XF, Zeng S. Optimal time to take once-daily oral medications in clinical practice. Int J Clin Pract 2008;62:1560-71.

Aboud HM, Ali AA, El-Menshawe SF, Elbary AA. Nanotransfersomes of carvedilol for intranasal delivery: formulation, characterization and in vivo evaluation. Drug Deliv 2015;23:1-11.

Aggarwal V, Kumar R, Sharma R, Singh Y, Teotia UV. Formulation and optimization of chronotherapeutic drug delivery from carvedilol sulphate compression coated tablets by using design of experiment approach. J Appl Pharm Sci 2013;3:141-6.

Singh DK, Yadav SA, Nigade SU, Poddar S, Kumar S. Fabrication of pulsatile delivery multiparticulate system of poorly water soluble carvidolol phosphate. Int Res J Pharm 2012;3:235-40.

Satwara RS, Patel PK. Formulation and optimization of chronomodulated press-coated tablet of carvedilol by box–behnken statistical design. ChronoPhysiol Ther 2012;2:35-50.

Patel P, Dhake A. Design and development of colon specific microspheres for chronotherapy of hypertension. J Pharm Bioallied Sci 2012;4:S33-4.

Singh DK, Kumar S, Poddar S. Development of biphasic pulsatile release mini-tablets system of poorly water soluble carvedilol phosphate. Int J Pharm Sci Res 2015;6:919-26.

Ganipisetty VN, Jalandhar D, Gnanadev G, Manoj P, Nadh RV. Novel reversed phase liquid chromatographic method for the simultaneously determination of potential impurities of bisoprolol fumarate and hydrochlorothiazide in a fixed dosage form. Sep Sci Technol 2016;51:1362-9.

Rousan TA, Mathew ST, Thadani U. The risk of cardiovascular side effects with anti-anginal drugs. Expert Opin Drug Saf 2016;15:1609- 23.

Rosenberg J, Gustafsson F. Bisoprolol for congestive heart failure. Expert Opin Pharmacother 2008;9:293-300.

Jagdale SC, Bari NA, Kuchekar BS, Chabukswar AR. Optimization studies on compression coated floating-pulsatile drug delivery of bisoprolol. BioMed Res Int 2013;2013:801769.

Lund IT, Bøckmann PL, Jacobsen EE. Highly enantioselective CALB-catalyzed kinetic resolution of building blocks for β-blocker atenolol. Tetrahedron 2016;72:7288-92.

Kannappan V, Mannemala SS. Simultaneous enantioseparation and purity determination of chiral switches of amlodipine and atenolol by liquid chromatography. J Pharm Biomed Anal 2016;120:221-7.

Khataee A, Lotfi R, Hasanzadeh A, Iranifam M, Joo SW. Flow-injection chemiluminescence analysis for sensitive determination of atenolol using cadmium sulfide quantum dots. Spectrochim Acta 2016;157:88- 95.

Amol M. Design and evaluation of pulsatile drug delivery system of atenolol for chronomodulated therapy. Int J Pharm Bio Sci 2012;3:1-8.

Keraliya RA, Patel MM. Effect of viscosity of hydrophilic coating polymer on lag time of atenolol pulsatile press coated tablets. J Pharm Chem 2014;1:15-21.

Bonthagarala B, Vadrevu S, Nama S, Sudarshan D, Nuthakki S. Formulation and evaluation of pulsatile drug delivery system of atenolol. Am J Biol Pharm Res 2014;1:28-33.

Jagdale SC, Sali MS, Barhate AL, Kuchekar BS, Chabukswar AR. Formulation, development, and evaluation of floating pulsatile drug delivery system of atenolol. PDA J Pharm Sci Technol 2013;67:214 28.

Sumer F, Colakoglu MK, Ozdemir Y, Ozsay O, İlter O, Bostanci EB, et al. Effect of nebivolol on liver regeneration in an experimental 70% partial hepatectomy model. Asian J Surg 2017;40:375-9.

Kim YJ, Kim HR, Jeon HJ, Ju HJ, Chung S, Choi DE, et al. Rhabdomyolysis in a patient taking nebivolol. Kidney Res Clin Pract 2016;35:182-6.

Cockcroft J. Nebivolol: a review. Expert Opin Pharmacother 2004;5:893-9.

Er E, Elikkan HC, Erk N. Highly sensitive and selective electrochemical sensor based on high quality graphene/nafion nanocomposite for voltammetric determination of nebivolol. Sens Actuators B Chem 2015;224:170-7.

Nayak M, Patel U, Bhimani B, Patel G, Chaudhry S. Formulation and evaluation of pulsatile tablet of nebivolol for chronopharmacotherapy of hypertension. Int J Pharm Res Biosci 2015;4:388-401.

Sandhya P, Jagathi T. Formulation development and in vitro evaluation of pulsatile drug delivery system of nebivolol hydrochloride. J Pharm 2015;2:81-90.

Shivakumar K, Sharma JV, Devi AN. Formulation and in-vitro characterization of nebivolol pulsatile drug delivery system. J Glob Trends Pharm Sci 2014;5:2204-10.

Beckerman J. Heart Disease and Beta-Blocker Therapy 2016 WebMD, LLC. Available from: http://www.webmd.com/heart-disease/guide/beta-blocker-therapy?print=true.

Hypertension (High Blood Pressure). U.S. National Library of Medicine. Rockville Pike, Bethesda: National Center for Biotechnology Information (NCBI).



How to Cite

SHRIVASTAVA, A. “PULSATILE DRUG DELIVERY SYSTEMS: A CASE OF BETA-BLOCKERS”. Asian Journal of Pharmaceutical and Clinical Research, vol. 12, no. 3, Mar. 2019, pp. 16-22, doi:10.22159/ajpcr.2019.v12i3.29704.



Review Article(s)